The long term goal of this investigation is an understanding of the function of basophilic leukocytes and mast cells in immunologic of both immediate and delayed type hypersensitivity, in neoplasia, and in normal physiology. Our aims over the next 5 year period are to better define the pathologic events of basophil/mastcell degranulation, and recovery from degranuation, that result from a variety of triggering stimuli and to establish whether these events result in different patterns of mediator (particularly histamine) release. The methods to be employed include immunofluorescence, transmission and scanning electron microscopy, energy dispersive microanalysis, and cytochemistry. These studies should enable us to test a model of basophil/mast cell degranulation that we have proposed to account for the varied rates of granule substance release that apparently occur under a variety of physiological and pathological circumstances. More specifically, we propose the following experiments: I. Additional structural studies of anaphylactic degranulation designed to evaluate the role of endocytosis, intracellular localization of calcium, membrane movements, cytoskeletal and cytomuscular elements, and plasma membrane esterases. II. Anatomic basis of several forms of non-anaphylactic basophil/mast cell degranulation including mediator release induced by lymphokines, strontium, D(2)0, and reserpine. III. Testing model of piece-meal basophil/mast cell degranulation using EM cytochemical methods.